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1.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360992

RESUMO

Several protocols exist for generating megakaryocytes (MKs) and platelets from human induced pluripotent stem cells (hiPSCs) with limited efficiency. We observed previously that mesoderm induction improved endothelial and stromal differentiation. We, therefore, hypothesized that a protocol modification prior to hemogenic endothelial cell (HEC) differentiation will improve MK progenitor (MKP) production and increase platelet output. We further asked if basic media composition affects MK maturation. In an iterative process, we first compared two HEC induction protocols. We found significantly more HECs using the modified protocol including activin A and CHIR99021, resulting in significantly increased MKs. MKs released comparable platelet amounts irrespective of media conditions. In a final validation phase, we obtained five-fold more platelets per hiPSC with the modified protocol (235 ± 84) compared to standard conditions (51 ± 15; p < 0.0001). The regenerative potency of hiPSC-derived platelets was compared to adult donor-derived platelets by profiling angiogenesis-related protein expression. Nineteen of 24 angiogenesis-related proteins were expressed equally, lower or higher in hiPSC-derived compared to adult platelets. The hiPSC-platelet's coagulation hyporeactivity compared to adult platelets was confirmed by thromboelastometry. Further stepwise improvement of hiPSC-platelet production will, thus, permit better identification of platelet-mediated regenerative mechanisms and facilitate manufacture of sufficient amounts of functional platelets for clinical application.


Assuntos
Plaquetas/citologia , Diferenciação Celular , Técnicas de Reprogramação Celular/métodos , Células-Tronco Pluripotentes Induzidas/citologia , Megacariócitos/citologia , Células Cultivadas , Meios de Cultura/química , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo
2.
Int J Mol Sci ; 22(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34445286

RESUMO

Extracellular vesicles (EVs) present a great potential for the development of new treatments in the biomedical field. To be used as therapeutics, many different sources have been used for EVs obtention, while only a few studies have addressed the use of platelet-derived EVs (pEVs). In fact, pEVs have been shown to intervene in different healing responses, thus some studies have evaluated their regenerative capability in wound healing or hemorrhagic shock. Even more, pEVs have proven to induce cellular differentiation, enhancing musculoskeletal or neural regeneration. However, the obtention and characterization of pEVs is widely heterogeneous and differs from the recommendations of the International Society for Extracellular Vesicles. Therefore, in this review, we aim to present the main advances in the therapeutical use of pEVs in the regenerative medicine field while highlighting the isolation and characterization steps followed. The main goal of this review is to portray the studies performed in order to enhance the translation of the pEVs research into feasible therapeutical applications.


Assuntos
Plaquetas/citologia , Vesículas Extracelulares/fisiologia , Medicina Regenerativa , Animais , Vesículas Extracelulares/transplante , Humanos , Medicina Regenerativa/métodos , Medicina Regenerativa/tendências , Choque Hemorrágico/fisiopatologia , Choque Hemorrágico/terapia , Cicatrização/fisiologia
4.
Clin Interv Aging ; 16: 1231-1239, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234423

RESUMO

Objective: Inflammation plays an important role in stroke. Many inflammatory markers in peripheral blood are proved to be associated with stroke severity or prognosis. But few comprehensive models or scales to evaluate the post-stroke depression (PSD) have been reported. In this study, we aimed to compare the level of systemic inflammation markers between PSD and non-PSD patients and explore the association of these inflammatory markers with PSD. Methods: Totally, 432 ischemic stroke patients were consecutively enrolled in the study and received 1 month follow-up. We used the 17-Hamilton Rating Scale to measure depressive symptoms at 1 month after stroke. With the Hamilton Depression Scale score of >7, patients were diagnosed with PSD. Systemic immune-inflammation index (SII), neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and derived neutrophil-to-lymphocyte ratio (dNLR) were calculated from the admission blood work. Results: Finally, 129 patients (30.5%) were diagnosed with PSD at 1 month. PSD patients showed significantly higher levels of SII (501.27 (345.43-782.58) vs 429.60 (315.64-570.98), P=0.001), NLR (2.36 (1.77-3.82) vs 2.17 (1.56-2.80), P=0.010), dNLR (1.67 (1.30-2.51) vs 1.54 (1.16-1.99), P=0.009), PLR (124.65 (95.25-155.15) vs 109.22 (92.38-142.03), P=0.015), especially SII at admission as compared to non-PSD patients. In the logistic analysis, SII value (>547.30) was independently associated with the occurrence of PSD (OR=2.181, 95% CI=1.274-3.732, p =0.004), better than dNLR (OR=1.833, 95% CI=1.071-3.137, p =0.027), PLR (OR= 1.822, 95% CI=1.063-3.122, p =0.029) and NLR (OR =1.728, 95% CI=1.009-2.958, p =0.046). Conclusion: Increased SII, PLR, dNLR, NLR, particularly SII at admission, are significantly correlated with PSD and may add some prognostic clues to find early discovery of PSD.


Assuntos
Depressão/etiologia , Depressão/fisiopatologia , Mediadores da Inflamação/metabolismo , Acidente Vascular Cerebral/complicações , Idoso , Biomarcadores , Plaquetas/citologia , Estudos de Coortes , Depressão/diagnóstico , Feminino , Humanos , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença
5.
FASEB J ; 35(8): e21818, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34320241

RESUMO

Fabry disease results from a deficiency of the lysosomal enzyme ⍺-Galactosidase-A (⍺-Gal A) and is estimated to occur in approximately 1:4100 live births. Characteristic of the disease is the accumulation of α-Gal-A substrates, primarily the glycosphingolipids (GSLs) globotriaosylceramide and globotriaosylsphingosine. Thrombotic events are a significant concern for Fabry patients, with strokes contributing to a significant decrease in overall lifespan. Currently, the mechanisms underlying the increased risk of thrombotic events experienced by Fabry patients are incompletely defined. Using a rat model of Fabry disease, we provide an improved understanding of the mechanisms linking GSL accumulation to thrombotic risk. We found that ⍺-Gal A-deficient rats accumulate myeloid-derived leukocytes at sites of GSL accumulation, including in the bone marrow and circulation, and that myeloid-derived leukocyte and megakaryocyte populations were prominent among cell types that accumulated GSLs. In the circulation, ⍺-Gal A-deficient rats had increases in cytokine-producing cell types and a corresponding elevation of pro-inflammatory cytokines. Lastly, circulating platelets from ⍺-Gal A-deficient rats accumulated a similar set of ⍺-Galactosidase-A substrates as was observed in megakaryocytes in the bone marrow, and exhibited increased platelet binding to fibrinogen in microfluidic and flow cytometric assays.


Assuntos
Plaquetas/citologia , Doença de Fabry/metabolismo , Células Mieloides/classificação , Células Mieloides/fisiologia , alfa-Galactosidase/metabolismo , Animais , Medula Óssea/enzimologia , Sistemas CRISPR-Cas , Feminino , Leucócitos/fisiologia , Masculino , Megacariócitos/fisiologia , Ativação Plaquetária , Agregação Plaquetária , Ratos , alfa-Galactosidase/genética
6.
Transfusion ; 61 Suppl 1: S243-S251, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269443

RESUMO

BACKGROUND: In traumatic bleeding, transfusion practice has shifted toward higher doses of platelets and plasma transfusion. The aim of this systematic review was to investigate whether a higher platelet-to-red blood cell (RBC) transfusion ratio improves mortality without worsening organ failure when compared with a lower ratio of platelet-to-RBC. METHODS: Pubmed, Medline, and Embase were screened for randomized controlled trials (RCTs) in bleeding trauma patients (age ≥16 years) receiving platelet transfusion between 1946 until October 2020. High platelet:RBC ratio was defined as being the highest ratio within an included study. Primary outcome was 24 hour mortality. Secondary outcomes were 30-day mortality, thromboembolic events, organ failure, and correction of coagulopathy. RESULTS: In total five RCTs (n = 1757 patients) were included. A high platelet:RBC compared with a low platelet:RBC ratio significantly improved 24 hour mortality (odds ratio [OR] 0.69 [0.53-0.89]) and 30- day mortality (OR 0.78 [0.63-0.98]). There was no difference between platelet:RBC ratio groups in thromboembolic events and organ failure. Correction of coagulopathy was reported in five studies, in which platelet dose had no impact on trauma-induced coagulopathy. CONCLUSIONS: In traumatic bleeding, a high platelet:RBC improves mortality as compared to low platelet:RBC ratio. The high platelet:RBC ratio does not influence thromboembolic or organ failure event rates.


Assuntos
Contagem de Eritrócitos , Hemorragia/sangue , Contagem de Plaquetas , Ferimentos e Lesões/sangue , Plaquetas/citologia , Eritrócitos/citologia , Hemorragia/mortalidade , Humanos , Ferimentos e Lesões/mortalidade
7.
Int J Mol Sci ; 22(12)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199303

RESUMO

The main purpose of new stent technologies is to overcome unfavorable material-related incompatibilities by producing bio- and hemo-compatible polymers with anti-inflammatory and anti-thrombogenic properties. In this context, wettability is an important surface property, which has a major impact on the biological response of blood cells. However, the influence of local hemodynamic changes also influences blood cell activation. Therefore, we investigated biodegradable polymers with different wettability to identify possible aspects for a better prediction of blood compatibility. We applied shear rates of 100 s-1 and 1500 s-1 and assessed platelet and monocyte activation as well as the formation of CD62P+ monocyte-bound platelets via flow cytometry. Aggregation of circulating platelets induced by collagen was assessed by light transmission aggregometry. Via live cell imaging, leukocytes were tracked on biomaterial surfaces to assess their average velocity. Monocyte adhesion on biomaterials was determined by fluorescence microscopy. In response to low shear rates of 100 s-1, activation of circulating platelets and monocytes as well as the formation of CD62P+ monocyte-bound platelets corresponded to the wettability of the underlying material with the most favorable conditions on more hydrophilic surfaces. Under high shear rates, however, blood compatibility cannot only be predicted by the concept of wettability. We assume that the mechanisms of blood cell-polymer interactions do not allow for a rule-of-thumb prediction of the blood compatibility of a material, which makes extensive in vitro testing mandatory.


Assuntos
Plaquetas/citologia , Comunicação Celular/efeitos dos fármacos , Monócitos/citologia , Monócitos/efeitos dos fármacos , Poliésteres/farmacologia , Plaquetas/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Agregação Plaquetária/efeitos dos fármacos , Água , Molhabilidade
8.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209789

RESUMO

Near-physiological in vitro thrombogenicity test systems for the evaluation of blood-contacting endothelialized biomaterials requires co-cultivation with platelets (PLT). However, the addition of PLT has led to unphysiological endothelial cell (EC) detachment in such in vitro systems. A possible cause for this phenomenon may be PLT activation triggered by the applied endothelial cell medium, which typically consists of basal medium (BM) and nine different supplements. To verify this hypothesis, the influence of BM and its supplements was systematically analyzed regarding PLT responses. For this, human platelet rich plasma (PRP) was mixed with BM, BM containing one of nine supplements, or with BM containing all supplements together. PLT adherence analysis was carried out in six-channel slides with plasma-treated cyclic olefin copolymer (COC) and poly(tetrafluoro ethylene) (PTFE, as a positive control) substrates as part of the six-channel slides in the absence of EC and under static conditions. PLT activation and aggregation were analyzed using light transmission aggregometry and flow cytometry (CD62P). Medium supplements had no effect on PLT activation and aggregation. In contrast, supplements differentially affected PLT adherence, however, in a polymer- and donor-dependent manner. Thus, the use of standard endothelial growth medium (BM + all supplements) maintains functionality of PLT under EC compatible conditions without masking the differences of PLT adherence on different polymeric substrates. These findings are important prerequisites for the establishment of a near-physiological in vitro thrombogenicity test system assessing polymer-based cardiovascular implant materials in contact with EC and PLT.


Assuntos
Materiais Biocompatíveis/farmacologia , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Meios de Cultura/farmacologia , Adulto , Materiais Biocompatíveis/química , Plaquetas/citologia , Meios de Cultura/química , Endotélio/citologia , Feminino , Humanos , Masculino , Teste de Materiais , Pessoa de Meia-Idade , Ativação Plaquetária/efeitos dos fármacos , Adesividade Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Polímeros/farmacologia , Tecidos Suporte/química
9.
Transfusion ; 61 Suppl 1: S68-S79, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269433

RESUMO

Although it is well established that transfusion of platelets in cases of severe bleeding reduces mortality, the availability of platelets is hampered by harsh restrictions on shelf life due to elevated risks of microbial contamination and functional losses with room temperature-stored platelets (RTP) kept at 22°C. In contrast, many recent studies have shown that 4°C cold-stored platelets (CSP) are able to overcome these shortcomings leading to the recent Food and Drug Administration licensure for 14-day stored CSP when conventional platelets are unavailable. This work expands the evidence supporting superiority of CSP function by assaying the less explored platelet-mediated clot retraction of RTP and CSP in either autologous plasma (AP) or platelet additive solution (PAS) for up to 21 days. The results demonstrate that CSP have better preservation of contractile function, exhibiting retraction for up to 21 days in both AP and PAS and forming highly ordered fibrin scaffolds similar to those of fresh platelets. In contrast, RTP stored in AP showed impaired contractile function by Day 5 with no retraction after 10 days, whereas PAS-stored RTP retained contractile function for up to 21 days. Collectively, these findings support extended storage of CSP and suggest that storage in PAS can mitigate functional losses in RTP.


Assuntos
Plaquetas/citologia , Preservação de Sangue/métodos , Coagulação Sanguínea , Plaquetas/metabolismo , Fibrina/metabolismo , Humanos , Testes de Função Plaquetária , Refrigeração , Temperatura
10.
Transfusion ; 61 Suppl 1: S275-S285, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269451

RESUMO

Platelet transfusions are an integral component of balanced hemostatic resuscitation protocols used to manage severe hemorrhage following trauma. Enhancing the hemostatic potential of platelets could lead to further increases in the efficacy of transfusions, particularly for non-compressible torso hemorrhage or severe hemorrhage with coagulopathy, by decreasing blood loss and improving overall patient outcomes. Advances in gene therapies, including RNA therapies, are leading to new strategies to enhance platelets for better control of hemorrhage. This review will highlight three approaches for creating modified platelets using gene therapies: (i) direct transfection of transfusable platelets ex vivo, (ii) in vitro production of engineered platelets from platelet-precursor cells, and (iii) modifying the bone marrow for in vivo production of modified platelets. In summary, modifying platelets to enhance their hemostatic potential is an exciting new frontier in transfusion medicine, but more preclinical development as well as studies testing the safety and efficacy of these agents are needed.


Assuntos
Plaquetas/metabolismo , Engenharia Genética , Hemostasia , Transfusão de Plaquetas , Animais , Plaquetas/citologia , Engenharia Genética/métodos , Terapia Genética/métodos , Humanos , Transfusão de Plaquetas/métodos , Transfecção
11.
Transfusion ; 61 Suppl 1: S58-S67, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269458

RESUMO

BACKGROUND: Refrigeration, or cold-storage, of platelets may be beneficial to extend the limited shelf-life of conventionally stored platelets and support transfusion protocols in rural and military areas. The aim of this study was to compare the morphologic, metabolic, and functional aspects of apheresis platelets stored at room-temperature (RT) or cold conditions, in either plasma or supplemented with platelet additive solution (PAS). STUDY DESIGN AND METHODS: Double-dose apheresis platelets were collected in either 100% plasma or 40% plasma/60% PAS-E using the Trima apheresis platform. One component from each group was either stored at RT (20-24°C) or refrigerated (2-6°C). Platelets were tested over a 21-day period. RESULTS: The platelet concentration decreased by approximately 30% in all groups during 21 days of storage (p > .05). Cold-storage reduced glycolytic metabolism, and the pH was maintained above the minimum specification (>6.4) for 21 days only when platelets were stored in PAS. The surface phenotype and the composition of the supernatant were differentially affected by temperature and storage solution. Functional responses (aggregation, agonist-induced receptor activation, clotting time) were improved during cold-storage, and the influence of residual plasma was assay dependent. CONCLUSION: In vitro platelet quality is differentially affected by storage time, temperature, and solution. Cold-storage, particularly in PAS, better maintains key metabolic, phenotypic, and functional parameters during prolonged storage.


Assuntos
Plaquetas/citologia , Preservação de Sangue/métodos , Plaquetas/metabolismo , Temperatura Baixa , Humanos , Testes de Função Plaquetária , Plaquetoferese , Refrigeração
12.
Transfusion ; 61 Suppl 1: S101-S110, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269459

RESUMO

BACKGROUND: There is a global increase in whole blood usage and at the same time, emerging pathogens give cause for pathogen reduction technology (PRT). The Mirasol PRT has shown promising results for plasma and platelet concentrate products. Treatment of whole blood with subsequent platelet survival and recovery analysis would be of global value. STUDY DESIGN AND METHODS: A two-arm, open-label laboratory study was performed with 40 whole blood collections in four groups: non-leukoreduced non-PRT-treated, non-leukoreduced PRT-treated, leukoreduced non-PRT-treated, and leukoreduced PRT-treated. Leukoreduction and/or PRT-treatment was performed on the day of collection, then all WB units were stored at room temperature for 24 h. Sampling was performed after hold-time and after 24-h storage in RT. If PRT-treatment or leukoreduction, samples were also taken subsequently after treatment. Thirteen healthy volunteer blood donors completed the in vivo study per protocol. All WB units were non-leukoreduced and PRT-treated. Radioactive labeling of platelets from RT-stored, PRT-treated whole blood, sampling of subjects, recovery, and survival calculations were performed according to the Biomedical Excellence for Safer Transfusion Collaborative protocol. RESULTS: In vitro characteristics show that PRT-treatment leads to increased levels of hemolysis, potassium, and lactate, while there are decreased levels of glucose, FVIII, and fibrinogen after 24 h of storage. All values are within requirements for WB. In vivo recovery and survival of platelets were 85.4% and 81.3% of untreated fresh control, respectively. CONCLUSIONS: PRT-treatment moderately reduces whole blood quality but is well within the limits of international guidelines. Recovery and survival of platelets are satisfactory after Mirasol treatment.


Assuntos
Plaquetas/efeitos dos fármacos , Plaquetas/efeitos da radiação , Segurança do Sangue , Fármacos Fotossensibilizantes/farmacologia , Riboflavina/farmacologia , Raios Ultravioleta , Plaquetas/citologia , Preservação de Sangue , Humanos , Testes de Função Plaquetária , Fatores de Tempo
13.
Transfusion ; 61 Suppl 1: S90-S100, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269461

RESUMO

BACKGROUND: Recent studies characterizing in vitro hemostatic properties of whole blood (WB) leukoreduced (LR) with a platelet-sparing filter have described subtle, if any, changes to viscoelastic clotting; however, reductions in platelet (PLT) content and impedance aggregometry (IA) responses have been noted. The effects of filtration of WB (i.e., filter-contact effects, reduction in platelet and leukocyte count) have not been rigorously investigated as to their individual impacts on platelet IA responses. STUDY DESIGN AND METHODS: WB units from healthy donors were collected and characterized to assess the effects of platelet-sparing leukoreduction (LR) upon the in vitro hemostatic measures of platelet IA and thromboelastometry. Further characterization of platelet IA responses was carried out in WB samples to delineate the effects of platelet count and leukocyte presence/absence upon the response. RESULTS: WB filtration reduced the platelet count and IA responses but had no impact on viscoelastic clotting measures in fresh WB. Experiments revealed that IA responses have a linear correlation with platelet count in both apheresis platelets and WB and that passage of platelets through the WB-LR filter has no impact upon the strength of this response. Further experiments in LR WB showed that addition of autologous leukocytes back to the platelets fully restored the platelet aggregation response to pre-filtration levels. CONCLUSION: WB filtration results in platelet count reduction and leukocyte removal; however, platelet IA is not degraded by passage through the filter. Apparent declines in platelet IA responses can be fully attributed to the reduction in platelet count and the removal of leukocytes.


Assuntos
Plaquetas/citologia , Leucócitos/citologia , Agregação Plaquetária , Hemostasia , Humanos , Procedimentos de Redução de Leucócitos , Contagem de Plaquetas , Testes de Função Plaquetária , Tromboelastografia
14.
Br J Haematol ; 194(3): 530-536, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34132393

RESUMO

COVID-19, caused by SARS-CoV-2, is a contagious life-threatening viral disease that has killed more than three million people worldwide to date. Attempts have been made to identify biomarker(s) to stratify disease severity and improve treatment and resource allocation. Patients with SARS-COV-2 infection manifest with a higher inflammatory response and platelet hyperreactivity; this raises the question of the role of thrombopoiesis in COVID-19 infection. Immature platelet fraction (IPF, %) and immature platelet counts (IPC, ×109 /l) can be used to assess thrombopoiesis. This study investigates whether the level of thrombopoiesis correlates with COVID-19 severity. A large cohort of 678 well-characterized COVID-19 patients was analyzed, including 658 (97%) hospitalized and 139 (21%) admitted to the intensive care unit (ICU). Elevated percentage IPF at presentation was predictive of length of hospitalization (P < 0·01) and ICU admission (P < 0·05). Additionally, percentage IPF at the peak was significantly higher among ICU patients than non-ICU patients (6·9 ± 5·1 vs 5·3 ± 8·4, P < 0·01) and among deceased patients than recovered patients (7·9 ± 6·3 vs 5·4 ± 7·8, P < 0·01). Furthermore, IPC at the peak was significantly higher among ICU patients than non-ICU patients (18·5 ± 16·2 vs. 13·2 ± 8·3, P < 0·05) and among patients on a ventilator than those not (22·1 ± 20·1 vs.13·4 ± 8·4, P < 0·05). Our study demonstrated that elevated initial and peak values of percentage IPF and IPC might serve as prognostic biomarkers for COVID-19 progression to severe conditions.


Assuntos
Plaquetas/patologia , COVID-19/patologia , Trombopoese , Idoso , Plaquetas/citologia , COVID-19/sangue , COVID-19/mortalidade , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
15.
PLoS One ; 16(6): e0252599, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34181675

RESUMO

Inflammation has an important role in the progression of various viral pneumonia, including COVID-19. Circulating biomarkers that can evaluate inflammation and immune status are potentially useful in diagnosing and prognosis of COVID-19 patients. Even more so when they are a part of the routine evaluation, chest CT could have even higher diagnostic accuracy than RT-PCT alone in a suggestive clinical context. This study aims to evaluate the correlation between inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelets-to-lymphocytes ratio (PLR), and eosinophils with the severity of CT lesions in patients with COVID-19. The second objective was to seek a statically significant cut-off value for NLR and PLR that could suggest COVID-19. Correlation of both NLR and PLR with already established inflammatory markers such as CRP, ESR, and those specific for COVID-19 (ferritin, D-dimers, and eosinophils) were also evaluated. One hundred forty-nine patients with confirmed COVID-19 disease and 149 age-matched control were evaluated through blood tests, and COVID-19 patients had thorax CT performed. Both NLR and PLR correlated positive chest CT scan severity. Both NLR and PLR correlated positive chest CT scan severity. When NLR value is below 5.04, CT score is lower than 3 with a probability of 94%, while when NLR is higher than 5.04, the probability of severe CT changes is only 50%. For eosinophils, a value of 0.35% corresponds to chest CT severity of 2 (Se = 0.88, Sp = 0.43, AUC = 0.661, 95% CI (0.544; 0.779), p = 0.021. NLR and PLR had significantly higher values in COVID-19 patients. In our study a NLR = 2.90 and PLR = 186 have a good specificity (0.89, p = 0.001, respectively 0.92, p<0.001). Higher levels in NLR, PLR should prompt the clinician to prescribe a thorax CT as it could reveal important lesions that could influence the patient's future management.


Assuntos
Plaquetas/citologia , COVID-19/diagnóstico por imagem , COVID-19/imunologia , Eosinófilos/citologia , Neutrófilos/citologia , Razão Sinal-Ruído , Tomografia Computadorizada por Raios X , Adulto , COVID-19/patologia , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade
16.
Eur Rev Med Pharmacol Sci ; 25(10): 3868-3878, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34109595

RESUMO

OBJECTIVE: This study aimed to compare the mortality rate between advanced-stage non-small cell lung cancer patients (NSCLC) with and without COVID-19. This study also explores the possible laboratory characteristics used for prognostication in patients with NSCLC and COVID-19. Additionally, this study evaluated potential differences in laboratory values between the case and control groups. PATIENTS AND METHODS: This is a single-center retrospective cohort study conducted in Dharmais National Cancer Hospital, Indonesia, enrolling patients with NSCLC undergoing chemotherapy or targeted therapy between May 2020 and January 2021. All patients with NSCLC and COVID-19 in these periods were enrolled into the case group. The control group was age-matched NSCLC patients without COVID-19 that was derived from the NSCLC cohort through randomization. RESULTS: There were 342 patients with NSCLC between May 2020 and January 2021. Twenty-seven (7.9%) of the patients were infected by COVID-19. To facilitate comparison, thirty-five age-matched controls with NSCLC were selected from the cohort. The mortality rate in patients with COVID-19 was 46.2%. Eleven patients (40.7%) had severe COVID-19, of which none survived. NLR >8.35 has a sensitivity of 83.3%, specificity of 92.9%, LR+ of 12, and LR- of 0.18. The AUC was 0.946 (95% CI 0.867-1.000), p<0.001. PLR >29.14 has a sensitivity of 75.0%, specificity of 71.4%, LR+ 2.62, LR- 0.35, and AUC 0.851 (95% CI 0.706-0.996), p=0.002. Both NLR and PLR were associated with shorter time-to-mortality in the unadjusted and adjusted model CONCLUSIONS: NLR and PLR are independent predictors of mortality in COVID-19 patients with NSCLC.


Assuntos
Plaquetas/citologia , COVID-19/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Linfócitos/citologia , Neutrófilos/citologia , Idoso , Área Sob a Curva , COVID-19/complicações , COVID-19/virologia , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Indonésia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Curva ROC , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Sensibilidade e Especificidade , Taxa de Sobrevida
17.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068404

RESUMO

Numerous cell-based therapeutics are currently being tested in clinical trials. Human platelet lysate (HPL) is a valuable alternative to fetal bovine serum as a cell culture medium supplement for a variety of different cell types. HPL as a raw material permits animal serum-free cell propagation with highly efficient stimulation of cell proliferation, enabling humanized manufacturing of cell therapeutics within a reasonable timeframe. Providers of HPL have to consider dedicated quality issues regarding identity, purity, potency, traceability and safety. Release criteria have to be defined, characterizing the suitability of HPL batches for the support of a specific cell culture. Fresh or expired platelet concentrates from healthy blood donors are the starting material for HPL preparation, according to regulatory requirements. Pooling of individual platelet lysate units into one HPL batch can balance donor variation with regard to essential platelet-derived growth factors and cytokines. The increasingly applied pathogen reduction technologies will further increase HPL safety. In this review article, aspects and regulatory requirements of whole blood donation and details of human platelet lysate manufacturing are presented. International guidelines for raw materials are discussed, and defined quality controls, as well as release criteria for safe and GMP-compliant HPL production, are summarized.


Assuntos
Plaquetas/citologia , Técnicas de Cultura de Células/normas , Diferenciação Celular , Animais , Proliferação de Células , Meios de Cultura , Humanos
18.
Radiol Oncol ; 55(3): 347-353, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34051707

RESUMO

BACKGROUND: The aim of the study was to evaluate pretreatment inflammatory markers as prognostic factors in patients with unresectable uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion. PATIENTS AND METHODS: 54 patients (44% male, median age: 61 years) were retrospectively assessed. A median of 3 (range: 1-11) treatment sessions were performed with melphalan (92%) or fotemustin (8%). Inflammatory indices were calculated as follows: neutrophils/nl to lymphocytes/nl ratio (NLR), systemic immune-inflammation index ([platelets/nl × neutrophils/nl]/[lymphocytes/nl]; SII), and platelets/nl to lymphocytes/nl ratio (PLR). The cut-off for dichotomization purposes was set at the median (inflammatory indices, hepatic tumor burden) or the upper level of normal. Kaplan Meier analysis was performed for median overall survival (OS) in months, and Cox proportional hazard model for uni(UVA) and multivariate (MVA) hazard ratio (HR, 95%CI) analyses were performed. RESULTS: Median OS of the study cohort was 7.7 (6.3-10.9) months. In UVA OS was prolonged for low C reactive protein (CRP) (13.5 vs. 5.2; p = 0.0005), low SII (10.8 vs. 5.6; p = 0.0005), low NLR (11.1 vs. 6.3; p = 0.0045), low aspartate aminotransferase (AST) (11.5 vs. 5.6; p = 0.015), alanine aminotransferases (ALT) (11.5 vs. 5.6; p = 0.01), and tumor burden ≦ 50% (8.2 vs. 4.8; p = 0.007). MVA confirmed low CRP (HR: 0.29, 0.11-0.7; p = 0.005), low SII (HR: 0.19, 0.11-0.7; p = 0.008), and low ALT (HR: 0.13, 0.02-0.63; p = 0.011) as independent predictors for prolonged OS. Patients with ≦ 1, 2, 3 elevated significant MVA-factors survived a median of 14.9, 7.7, and 3.9 months, respectively (p = 0.0001). CONCLUSIONS: Pretreatment inflammatory markers (CRP, SII) and AST were independent prognostic survival markers in patients with uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion. A combination of factors may help to identify patients potentially benefitting from treatment.


Assuntos
Neoplasias Hepáticas/sangue , Melanoma/sangue , Neoplasias Uveais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Antineoplásicos/uso terapêutico , Aspartato Aminotransferases/sangue , Biomarcadores Tumorais/sangue , Plaquetas/citologia , Proteína C-Reativa/análise , Quimioterapia do Câncer por Perfusão Regional/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Linfócitos/citologia , Masculino , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Melanoma/secundário , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Neutrófilos/citologia , Compostos de Nitrosoureia/uso terapêutico , Compostos Organofosforados/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Carga Tumoral , Neoplasias Uveais/sangue
19.
Cell Biol Int ; 45(9): 1832-1850, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33945651

RESUMO

December 2019 will never be forgotten in the history of medicine when an outbreak of pneumonia of unknown etiology in Wuhan, China sooner or later prompted the World Health Organization to issue a public health warning emergency. This is not the first nor will it be the last time that a member of ß-coronaviruses (CoVs) is waging a full-scale war against human health. Notwithstanding the fact that pneumonia is the primary symptom of the novel coronavirus (2019nCoV; designated as SARS-CoV-2), the emergence of severe disease mainly due to the injury of nonpulmonary organs at the shadow of coagulopathy leaves no choice, in some cases, rather than a dreadful death. Multiple casual factors such as inflammation, endothelial dysfunction, platelet and complement activation, renin-angiotensin-aldosterone system derangement, and hypoxemia play a major role in the pathogenesis of coagulopathy in coronavirus disease 2019 (COVID-19) patients. Due to the undeniable role of coagulation dysfunction in the initiation of several complications, assessment of coagulation parameters and the platelet count would be beneficial in early diagnosis and also timely prediction of disease severity. Although low-molecular-weight heparin is considered as the first-line of treatment in COVID-19-associated coagulopathy, several possible therapeutic options have also been proposed for better management of the disease. In conclusion, this review would help us to gain insight into the pathogenesis, clinical manifestation, and laboratory findings associated with COVID-19 coagulopathy and would summarize management strategies to alleviate coagulopathy-related complications.


Assuntos
Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , COVID-19/patologia , Transtornos da Coagulação Sanguínea/etiologia , Plaquetas/citologia , Plaquetas/metabolismo , COVID-19/complicações , COVID-19/virologia , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Inflamação/etiologia , SARS-CoV-2/isolamento & purificação , Tromboembolia/tratamento farmacológico , Tromboembolia/etiologia
20.
Biomed Res Int ; 2021: 9678363, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33997045

RESUMO

Background: The preoperative platelet-to-lymphocyte ratio (PLR) evaluates the prognosis of gastric cancer patients. However, whether preoperative PLR may be used to evaluate the prognosis of mucinous gastric carcinoma (MGC) patients is poorly investigated. The present study evaluated the effect of preoperative PLR on overall survival in gastric cancer patients with a mucinous component. Methods: A total of 336 MGC were enrolled in this study, and the characteristics of the tumor, including pathological features and clinical data, were retrospectively analyzed. Results: A high PLR was associated with larger tumor size, advanced tumor invasion, lymph node metastasis, advanced TNM stage, tumor location, total gastrectomy, low hemoglobin level, low albumin level, high fibrinogen level, high platelet level, and high neutrophil-to-lymphocyte ratio (NLR, all P's < 0.05). Multivariate analysis identified age (HR = 1.876; 95% CI 1.361-2.585, P < 0.001), TNM stage (HR = 2.350; 95% CI 1.216-4.542, P = 0.011), globulin (HR = 1.520; 95% CI 1.067-2.165, P = 0.020), total gastrectomy (HR = 0.537; 95% CI 0.373-0.772, P = 0.001), and PLR (HR = 1.582; 95% CI 1.066-2.348, P = 0.023) as independent prognostic factors for OS. Conclusion: Preoperative PLR is related to pathological features and may independently evaluate the survival of MGC. Therefore, preoperative PLR may help physicians develop treatment plans and evaluate survival in these patients.


Assuntos
Plaquetas/citologia , Linfócitos/citologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Análise de Sobrevida
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